Abstract
The near-infrared photoluminescence intrinsic to semiconducting single-walled carbon nanotubes is ideal for biological imaging owing to the low autofluorescence and deep tissue penetration in the near-infrared region beyond 1 µm. However, biocompatible single-walled carbon nanotubes with high quantum yield have been elusive. Here, we show that sonicating single-walled carbon nanotubes with sodium cholate, followed by surfactant exchange to form phospholipid–polyethylene glycol coated nanotubes, produces in vivo imaging agents that are both bright and biocompatible. The exchange procedure is better than directly sonicating the tubes with the phospholipid–polyethylene glycol, because it results in less damage to the nanotubes and improves the quantum yield. We show whole-animal in vivo imaging using an InGaAs camera in the 1–1.7 µm spectral range by detecting the intrinsic near-infrared photoluminescence of the ‘exchange’ single-walled carbon nanotubes at a low dose (17 mg l−1 injected dose). The deep tissue penetration and low autofluorescence background allowed high-resolution intravital microscopy imaging of tumour vessels beneath thick skin.
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Liu, Z., Tabakman, S., Welsher, K. & Dai, H. Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. Nano Res. 2, 85–175 (2009).
Dhar, S. et al. Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device. J. Am. Chem. Soc. 130, 11467–11476 (2008).
Liu, Z., Winters, M., Holodniy, M. & Dai, H. J. siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew Chem. Int. Ed. 46, 2023–2027 (2007).
Liu, Z. et al. Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res. 68, 6652–6660 (2008).
Liu, Z. et al. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nature Nanotech. 2, 47–52 (2007).
Liu, Z. et al. Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc. Natl Acad. Sci. USA 105, 1410–1415 (2008).
De La Zerda, A. et al. Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nature Nanotech. 3, 557–562 (2008).
Cherukuri, P., Bachilo, S. M., Litovsky, S. H. & Weisman, R. B. Near-infrared fluorescence microscopy of single-walled carbon nanotubes in phagocytic cells. J. Am. Chem. Soc. 126, 15638–15639 (2004).
Cherukuri, P. et al. Mammalian pharmacokinetics of carbon nanotubes using intrinsic near-infrared fluorescence. Proc. Natl Acad. Sci. USA 103, 18882–18886 (2006).
Leeuw, T. K. et al. Single-walled carbon nanotubes in the intact organism: near-IR imaging and biocompatibility studies in Drosophila. Nano Lett. 7, 2650–2654 (2007).
Welsher, K., Liu, Z., Daranciang, D. & Dai, H. Selective probing and imaging of cells with single walled carbon nanotubes as near-infrared fluorescent molecules. Nano Lett. 8, 586–590 (2008).
Chen, Z. et al. Protein microarrays with carbon nanotubes as multicolor Raman labels. Nature Biotechnol. 26, 1285–1292 (2008).
O'Connell, M. J. et al. Band gap fluorescence from individual single-walled carbon nanotubes. Science 297, 593–596 (2002).
Aubin, J. E. Autofluorescence of viable cultured mammalian cells. J. Histochem. Cytochem. 27, 36–43 (1979).
Britton, C. Near-infrared images using continuous, phase-modulated, and pulsed light with quantitation of blood and blood oxygenation. Ann. NY Acad. Sci. 838, 29–45 (1998).
Lim, Y. T. et al. Selection of quantum dot wavelengths for biomedical assays and imaging. Mol. Imag. 2, 50–64 (2003).
Kam, N. W. S., O'Connell, M., Wisdom, J. A. & Dai, H. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc. Natl Acad. Sci. USA 102, 11600–11605 (2005).
Wenseleers, W. et al. Efficient isolation and solubilization of pristine single-walled nanotubes in bile salt micelles. Adv. Funct. Mater. 14, 1105–1112 (2004).
Hertel, T. et al. Spectroscopy of single- and double-wall carbon nanotubes in different environments. Nano Lett. 5, 511–514 (2005).
Chiashi, S., Watanabe, S., Hanashima, T. & Homma, Y. Influence of gas adsorption on optical transition energies of single-walled carbon nanotubes. Nano Lett. 8, 3097–3101 (2008).
Liu, Z., Sun, X., Nakayama-Ratchford, N. & Dai, H. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS Nano 1, 50–56 (2007).
Heller, D. A. et al. Concomitant length and diameter separation of single-walled carbon nanotubes. J. Am. Chem. Soc. 126, 14567–14573 (2004).
Cognet, L. et al. Stepwise quenching of exciton fluorescence in carbon nanotubes by single-molecule reactions. Science 316, 1465–1468 (2007).
Georgi, C. et al. Photoinduced luminescence blinking and bleaching in individual single-walled carbon nanotubes. ChemPhysChem 9, 1460–1464 (2008).
Saito, R., Dresselhaus, G. & Dresselhaus, M. S. Physical Properties of Carbon Nanotubes (Imperial College Press, 1998).
Kedrin, D. et al. Intravital imaging of metastatic behavior through a mammary imaging window. Nature Meth. 5, 1019–1021 (2008).
Lehr, H. A. et al. Dorsal skinfold chamber technique for intravital microscopy in nude mice. Am. J. Pathol. 143, 1055–1062 (1993).
Jain, R. K., Munn, L. L. & Fukumura, D. Dissecting tumour pathophysiology using intravital microscopy. Nature Rev. Canc. 2, 266–276 (2002).
Acknowledgements
The authors would like to thank X. Chen for the RGD peptide. This work was supported partially by CCNE-TR at Stanford University, NIH-NCI RO1 CA135109-02 and Ensysce.
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K.W., Z.L., S.S., J.R., D.D. and H.D. conceived and designed the experiments. K.W., Z.L., S.S., J.R. and Z.C. performed the experiments. K.W. analysed the data. K.W. and H.D. co-wrote the paper.
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Welsher, K., Liu, Z., Sherlock, S. et al. A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice. Nature Nanotech 4, 773–780 (2009). https://doi.org/10.1038/nnano.2009.294
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DOI: https://doi.org/10.1038/nnano.2009.294
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